The interaction between nmda-receptor activation and the polymerization statae of actin in cultured hippocampal neurones

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Project objective

The level at which signal-transduction is integrated to give Long-term-potentiation (LTP) is unclear, however, recent evidence implicates the cytoskeleton as important. The characteristic ATP-, calcium-dependent rundown of the NMDA-receptor (which is centrally involved in LTP) is reversed by treatments thought to specifically protect the filamentous state of the cytoskeletal protein actin (F-actin) from depolymerization into its monomeric components (G-actin). Since F-actin depolymerization is regulated by calcium-dependent proteases it is thought that the receptor rundown could be through NMDA-receptor activated cytosolic calcium increases. Currently, there are no studies demonstrating a direct effect of NMDA-receptor stimulation on the state of F-actin. This project will directly determine whether such a link exists, and whether treatments thought to alter the polymerisation state of actin are effective. We will use cultured neurones of the rat hippocampus, and the site-selective probes: phalloidin for F-(polymerized), and DNAaseI for G-(depolymerized) actin. Fluorescent conjugates of these probes will allow visualisation of F-, and G-actin simultaneously in Axed, and living neuronal cells. The distribution and intensity of staining will be monitored in single cells using confocal microscopy after systematic treatments.

Original text from CORDIS.

Participants

• INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE · PARISCoordinatorFrance
• Not availableCity levelUnited Kingdom

Links

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